Microvascular Blood Flow in Sickle Cell Anemia

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Sickle cell disease (SCD) is an inherited blood disorder that causes the red blood cells to change their shape from a round shape to a half-moon/crescent or sickled shape. Sickle-shaped cells can cause problems by getting stuck in blood vessels, blocking blood flow, and can cause inflammation and injury to important body parts. There are no specific treatments that improve this condition and promote blood flow hindered by sickle cell blockages. Another big challenge in managing sickle cell disease is that there are no good measures to determine changes and improvements in blood flow.

Contrast-enhanced ultrasound is a technique currently used to detect blood flow in the heart, muscles, and other organs. It is extremely sensitive and can detect blood flow in the smallest of blood vessels. It would be very useful in helping healthcare providers know whether treatment strategies are improving blood flow during sickle cell blockages.

The hypothesis is that contrast-enhanced ultrasound will be a feasible tool for determining changes in blood flow of subjects with sickle cell disease.

Sickle cell disease is an inherited blood disorder that affects one of every 400 African-Americans newborns in the United States. Sickle cell disease causes the red blood cells to change their shape from a round shape to a half-moon sickle shape. Individuals who have sickle cell disease have a different type of protein that carries oxygen in the blood (hemoglobin) than individuals without sickle cell disease. This different type of hemoglobin makes the red blood cell change into a crescent shape under certain conditions. Sickle shaped cells are a problem because the often get stuck on blood vessels blocking the flow of blood, and cause inflammation and injury to important areas of the body. These symptoms can lead to a painful occurrence called a "sickle cell crisis". Many individuals have to be admitted into the hospital because of the pain caused by a sickle cell crisis.

Regadenoson is a drug that may help prevent inflammation and injury caused by the sickle shaped cells. This drug is approved by the FDA to be used as a bolus during a heart stress test in people unable to exercise enough to put stress on the heart by making it beat faster. In a recent Phase I study, a safe dose for regadenoson was determined for adults with sickle cell disease. This dose was given by a slow IV infusion for a 24-48 hour period.

Hydroxyurea is the only FDA approved drug for the treatment of sickle cell disease. Hydroxyurea is a pill taken orally and works well but is not useful during a severe sickle cell crisis.

In this study researchers will use a new method, contrast-enhanced ultrasound (CEU), to visualize tiny blood vessels in cardiac and skeletal muscle. Changes in CEU measurements before, during and after administration of regadenoson will be examined. Contrast-enhanced ultrasounds will also be performed in individuals who are not having a sickle cell crisis. Some of those individuals will also undergo CEU while they are having a sickle cell crisis to compare those measurements . Lastly CEU results will be compared between individuals with sickle cell anemia and healthy African-Americans. These CEU's will be used to determine if there are changes in the blood flow of tiny blood vessels in certain conditions.

This study wants to know if this new method of contrast-enhanced ultrasound will be a useful tool for physicians to use in individuals with sickle cell anemia. The researchers also want to determine if this new method of CEU can be used to reveal if some treatments for sickle cell anemia work better than others.

Subjects who are not having a pain crisis will have contrast-enhanced ultrasound performed up to four times over a two-day period. Time points will resemble the time course used for the Regadenoson Arm, although no investigational drug will be given.

Microvascular Blood Flow in Sickle Cell Anemia with Regadenoson Use [ Time Frame: 5 years ]

To determine changes in microvascular blood flow using contrast-enhanced ultrasound in adults with sickle cell anemia before, during and after a 24 hour infusion of regadenoson

Secondary Outcome Measures
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Changes in Microvascular Blood Flow in Subjects with Sickle Cell Anemia During a Pain Crisis [ Time Frame: 5 years ]

To examine differences in microvascular blood flow using contrast-enhanced ultrasound in adults with sickle cell anemia at a baseline state, and also comparing to contrast-enhanced ultrasound measurements during a pain crisis

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Ages Eligible for Study:

18 Years to 70 Years (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Regadenoson ARM Inclusion Criteria:

Diagnosis of sickle cell anemia confirmed by hemoglobin analysis

Ages 18 to 70 years

Subjects must have laboratory indices as outlined by the protocol

Reliable IV access as determined by physician

Sickle Cell Controls ARM Inclusion Criteria:

Diagnosis of sickle cell anemia confirmed by hemoglobin analysis

Ages 18 to 70 years

Sickle Cell CEU ARM Inclusion Criteria:

Diagnosis of sickle cell anemia, confirmed by hemoglobin analysis

Males and females age 18-70 years

Healthy Control ARM Inclusion Criteria:

African American

Ages 18 to 70 years

Technique Optimization Control ARM Inclusion Criteria:

-Ages 18 to 70 years

Exclusion Criteria:

Regadenoson ARM Exclusion Criteria

Hospitalization, emergency department visit or self-reported crisis within last 2 weeks for any reason or 4 weeks from acute chest syndrome

Current physician diagnosis of active asthma (within last 12 months) or current use of asthma medications

Second or third degree AV block or sinus node dysfunction

Known or suspected right to left sided cardiac shunts

History of a bleeding diathesis

History of clinically overt stroke

History of severe hypertension not adequately controlled with anti-hypertensive medications

Receiving chronic anti-coagulation or anti-platelet therapy

History of metastatic cancer

Receiving other investigational study agents, or have received a study agent in the last 30 days

Uncontrolled intercurrent illness

Pregnant or breastfeeding women

Subjects who have a HIV infection

Subjects who have had a hematopoietic stem cell transplant

Subjects who are taking medications that may interact with the investigational agent

Prior hypersensitivity reactions to either regadenoson or ultrasound contrast agents

Sickle Cell Controls Exclusion Criteria:

Hospitalization, emergency department visit or self-reported crisis within last 2 weeks for any reason or 4 weeks from acute chest syndrome

Known pregnancy

Known history of HIV

Known or suspected right to left sided cardiac shunts

Receiving other investigational study agents, or have received a study agent within the last 30 days

Subjects who have had a hematopoietic stem cell transplant

Prior hypersensitivity reactions to ultrasound contrast agents

History of severe hypertension not adequately controlled with anti-hypertensive medications

Uncontrolled intercurrent illness

Sickle Cell CEU ARM Exclusion Criteria:

Pregnant women

Subjects who have a HIV infection

History of stem cell transplant

Current involvement in a therapeutic clinical trial

Known or suspected right to left sided cardiac shunts

Prior hypersensitivity reactions to ultrasound contrast agents

History of severe hypertension not adequately controlled with anti-hypertensive medications

Uncontrolled intercurrent illness

Healthy Control ARM Exclusion Criteria:

Sickle cell disease or sickle cell trait

Known or suspected right to left sided cardiac shunts

Diagnosis of type 1 or type 2 diabetes mellitus

Hypertension

History or current diagnosis of dyslipidemia or taking lipid lowering drugs